Abstract
Photodynamic therapy (PDT) relies on the administration of a photosensitizer (PS) that is activated, after a certain drug-to-light interval (DLI), by the irradiation of the target tumour with light of a specific wavelength absorbed by the PS. Typically, low light doses are insufficient to eradicate solid tumours and high fluence rates have been described as poorly immunogenic. However, previous work with mice bearing CT26 tumours demonstrated that vascular PDT with redaporfin, using a low light dose delivered at a high fluence rate, not only destroys the primary tumour but also reduces the formation of metastasis, thus suggesting anti-tumour immunity. This work characterizes immune responses triggered by redaporfin-PDT in mice bearing CT26 tumours. Our results demonstrate that vascular-PDT leads to a strong neutrophilia (2–24 h), systemic increase of IL-6 (24 h), increased percentage of CD4+ and CD8+ T cells producing IFN-γ or CD69+ (2–24 h) and increased CD4+/CD8+ T cell ratio (2–24 h). At the tumour bed, T cell tumour infiltration disappeared after PDT but reappeared with a much higher incidence one day later. In addition, it is shown that the therapeutic effect of redaporfin-PDT is highly dependent on neutrophils and CD8+ T cells but not on CD4+ T cells.
Highlights
Photodynamic therapy (PDT) combines a photosensitizer (PS) molecule, red or infrared light and molecular oxygen, none of them being individually toxic, to treat solid tumours with selectivity and reduced adverse effects
Redaporfin-vascular-PDT is currently in phase I/II clinical trials for head and neck cancer which prompted the use of Balb/c mice bearing CT26.WT tumours as the preclinical model
Population had a minimal impact on the tumour growth kinetics that was not statistically significant (Figure 5). These findings suggest that cytotoxic T cells have a major role in the development of the anti-tumour immune response elicited by redaporfin-PDT, while helper T cells may have just a supportive role
Summary
Photodynamic therapy (PDT) combines a photosensitizer (PS) molecule, red or infrared light and molecular oxygen, none of them being individually toxic, to treat solid tumours with selectivity and reduced adverse effects. The redaporfin-PDT protocol applied low light doses (50 J/cm2) and high fluence rates (130 mW/cm2), 67% of the cured mice were protected from developing a new tumour after re-challenge with the same cancer cells on the contra-lateral thigh. Other insightful investigations on the stimulation of anti-tumour immunity with vascular-PDT include the studies by Hamblin and co-workers using verteporfin [10,21,22] and by Scherz and co-workers using padeliporfin [5]. Numerous studies in cancer immunotherapy (including within the PDT field) have described anti-tumour immune responses. In view of the importance of systemic immune responses and possible availability of blood samples, our study aimed at detecting signs of immune modulation at the blood of mice submitted to a vascular protocol of redaporfin-PDT. The changes in populations of neutrophils, CD8+ T cells and CD4+ T cells observed in the peripheral blood further motivated an assessment of the depletion of such cells
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